- Available:In stock1458
- Availability date:2020-07-30
- Dosage form:Bottle
- In stock:1458 Items
medroxyprogesterone acetate (17a-hydroxy-6a-methylprogesterone acetate) is a derivative of progesterone.
Medroxyprogesterone acetate is a synthetic progestin that resembles the endogenous hormone progesterone in its structure. The following pharmacological effects on the endocrine system were noted:
- inhibition of the synthesis of pituitary gonadotropic hormones (FSH and LH);
- a decrease in the levels of ACTH and hydrocortisone in the blood;
- a decrease in the level of circulating testosterone;
- a decrease in the level of circulating estrogen (due to inhibition of FSH synthesis and enzymatic induction of reductase in the liver, which leads to an increase in testosterone clearance and, as a result, a decrease in the conversion of androgens to estrogens).
All this leads to a number of pharmacological effects described above.
Medroxyprogesterone acetate, when administered parenterally in women at the recommended dose, inhibits the secretion of gonadotropic hormones, which prevents follicle maturation and the onset of ovulation and leads to thinning of the endometrium.
Medroxyprogesterone acetate, when administered orally or parenterally in the recommended doses in women with a sufficient level of endogenous estrogen, leads to the conversion of the proliferative endometrium into a secretory one. Its androgenic and anabolic effects are noted, but it is obvious that this drug does not have significant estrogenic activity. Whereas with parenteral administration of medroxyprogesterone, acetate suppresses the formation of gonadotropic hormones, which, in turn, prevents follicle maturation and the onset of ovulation. Data available today suggests that this does not occur with a single daily intake of the usual recommended oral daily dose.
Medroxyprogesterone acetate has antitumor activity. When patients use medroxyprogesterone acetate in high doses (via oral or intramuscular injection), it is effective in the palliative treatment of malignant hormone-dependent neoplasms.
The study of bone mineral density
Changes in bone mineral density in adult women
In a controlled clinical study in adult women who received injections of medroxyprogesterone acetate (IM at a dose of 150 mg) for a period of up to 5 years for contraception, a decrease in the mineral density of the bone tissue of the spine and thigh by an average of 5-6% was noted compared with the absence of significant changes in bone mineral density in the control group. The decrease in bone mineral density was more pronounced in the first 2 years of use of the drug and less in the following years. In 1; 2; 3; At 4 and 5 years of use, the average values of changes in the mineral density of bone tissue of the lumbar spine were −2.86, respectively; −4.11; −4.89; −4.93 and −5.38%. The average decrease in the mineral density of the bone tissue of the thigh as a whole and of the femoral neck was approximately the same.
After the cessation of injections of medroxyprogesterone acetate (IM at a dose of 150 mg), a gradual restoration of bone mineral density to baseline levels was noted over a 2-year period after treatment. 2 years after the cessation of treatment, the deficiency of bone mineral density in the spine and thigh decreased to about 2.1%. Longer treatment was associated with a slower rate of restoration of bone mineral density (see SPECIAL INSTRUCTIONS).
Changes in bone mineral density in adolescent girls (ages 12–18)
An open, non-randomized clinical trial of injections of medroxyprogesterone acetate (IM at a dose of 150 mg every 3 months for a period of up to 240 weeks [4.6 years]) in teenage girls (aged 12-18 years) for contraception also showed a significant decrease bone mineral density relative to baseline. Among girls who received ≥4 injections over a 60-week period, the average decrease in bone mineral density of the lumbar spine was −2.1% after 240 weeks; the average decrease for the hip in general and the hip neck in particular was −6.4 and −5.4%, respectively. Based on the average indicators of changes, further observation after treatment showed that after cessation of treatment, the mineral density of the bone tissue of the lumbar spine was restored to its original level after 1 year, and the mineral density of the bone tissue of the thigh - after about 3 years. Conversely, in patients who were not compared and who did not receive treatment, the average increase in bone mineral density after 240 weeks was 6.4, respectively; 1.7 and 1.9% for the lumbar spine, thigh in general, and the femoral neck in particular (see SPECIAL INSTRUCTIONS).
Womens Health Initiative Study
The Womens Health Initiative study on conjugated equine estrogens (0.625 mg) / medroxyprogesterone acetate (2.5 mg) to assess the risks and benefits of this combination therapy compared to placebo to prevent the development of certain chronic diseases was conducted with 16 608 women in the postmenopausal period at the age of 50–79 years with the intact uterus at the initial level. The primary endpoint was the incidence of coronary heart disease (non-fatal myocardial infarction and fatal outcome associated with coronary artery disease), and invasive breast cancer was considered as the primary undesirable result. The study was stopped ahead of schedule during the follow-up period, which averaged 5.2 years (planned duration 8.5 years), because, in accordance with the pre-established criterion for terminating the study, the increased risk of developing breast cancer and cardiovascular events outweighed this benefits included in the overall indicator (see SPECIAL INSTRUCTIONS).
Combination therapy with conjugated equine estrogens / medroxyprogesterone acetate caused a significant reduction in fracture rate due to osteoporosis (23%) and the total fracture rate (24%).
The Million Women Study
The Million Women Study is a prospective cohort study conducted in the UK with 1,084,110 women aged 50–64 years, of which 828,923 were included in the main breast cancer risk analysis some time after menopause. hormone therapy. In general, 50% of the studied population at a certain point in time used hormonal therapy. Patients who received hormone replacement therapy at baseline used drugs containing only estrogen (41%) or a combination of estrogen and progestin (50%). The average follow-up period was 2.6 years for analyzing cancer incidence and 4.1 years for mortality analysis (see SPECIAL INSTRUCTIONS).
A study of the effects of estrogen / progestin replacement therapy on the heart (HERS and HERS II studies) consisted of 2 randomized, prospective secondary prevention trials that examined the long-term effects of continuous oral combination therapy with conjugated equine estrogens / medroxyprogesterone acetate (0.625 mg conjugated equine estrogens and 2.5 mg medroxyprogesterone acetate) in women with coronary heart disease during postmenopause (see SPECIAL INSTRUCTIONS).This study included 2763 postmenopausal women with an intact uterus (mean age 66.7 years). The average follow-up period was 4.1 years for the HERS study and 2.7 years (for a total of 6.8 years) for the HERS II study (see SPECIAL INSTRUCTIONS).
Memory Study of the Womens Health Initiative
A memory study of the Womens Health Initiative, which was a sub-study of the Womens Health Initiative, included 4,532 predominantly healthy women 65–79 years postmenopausal and evaluated the effects of conjugated equine estrogen / medroxyprogesterone acetate therapy (0.625 mg conjugated equine estrogens and 2.5 mg medroxyprogesterone acetate) or conjugated equine estrogens only (0.625 mg) per frequency of possible dementia compared with placebo. The average follow-up period was 4.05 years for the administration group of conjugated equine estrogens / medroxyprogesterone acetate (see SPECIAL INSTRUCTIONS).
Pharmacokinetics Absorption After the intramuscular administration of medroxyprogesterone, acetate is slowly released, which ensures low but constant blood levels. Immediately after the administration of medroxyprogesterone acetate at a dose of 150 mg / ml, its plasma level was 1.7 ± 0.3 nmol / L. After 2 weeks, this level was 6.8 ± 0.8 nmol / L. After administration, the average time to reach peak concentration is approximately 4–20 days. The concentration of medroxyprogesterone acetate in the blood plasma gradually decreases and remains at a relatively constant level (approximately 1 ng / ml) for 2-3 months. The level of the drug in the blood can be determined within 7-9 months after administration of the drug.
Distribution. Medroxyprogesterone acetate is approximately 90–95% bound to protein. The volume of distribution is 20 ± 3.0 l. Medroxyprogesterone acetate crosses the BBB and the placental barrier (see Use during pregnancy and lactation). In breast milk of women who were breast-fed and received IM injections of medroxyprogesterone acetate at a dose of 150 mg, a low level of medroxyprogesterone acetate was determined (see Use during pregnancy and lactation).
Metabolism. Medroxyprogesterone acetate is metabolized in the liver.
Breeding. T½ after a single injection of the drug is approximately 6 weeks. Medroxyprogesterone acetate is excreted mainly with feces by biliary secretion. About 30% of the intramuscular dose is excreted in the urine after 4 days.
Gynecology: treatment of endometriosis.
recurrent and / or metastatic breast cancer;
recurrent and / or metastatic endometrial cancer;
recurrent and / or metastatic kidney cancer;
metastatic prostate cancer.
To make sure that the dose that is used is a homogeneous suspension of Depot-Prover, a sterile aqueous suspension of Depo-Prover should be thoroughly shaken immediately before use.
Doses need to be entered deeply in oil. You must be sure that the injection is carried out in muscle tissue, preferably in the gluteus maximus muscle, but other muscles, such as the deltoid, can also be used.
Before the injection, the injection site should be cleaned using standard methods.
The recommended dose of suspension for injection is 150 mg once every 3 months (12–13 weeks). Immediately before use, the suspension for injection should be shaken to ensure that the dose is administered as a uniform suspension. The drug is injected intramuscularly into the gluteus or deltoid muscle. The suspension for intramuscular administration is not intended for subcutaneous administration.
First injection.The initial injection should be carried out during the first 5 days after the start of the normal menstrual cycle, during the first 5 days after birth, if the patient does not breast-feed; if the patient is breastfeeding, 6 weeks after birth or later.
The second and subsequent injections. If the interval between intramuscular injections is more than 13 weeks, the possibility of pregnancy before the next injection should be excluded.
The transition from other methods of contraception. When switching from other methods of contraception, the drug should be injected in such a way as to ensure continuous contraception based on the mechanism of action of both methods (for example, patients who switch from oral contraceptives should receive the first injection of the drug within 7 days after taking the last tablet with the active substance) .
In the case of combined estrogen / progestin therapy for the treatment of women in the postmenopausal period, the drug should be used in the minimum effective dose and for the shortest possible period in accordance with the purpose of treatment and taking into account the health risks of an individual patient; the appropriateness of such therapy should be periodically evaluated.
It is recommended to conduct periodic examinations, which in frequency and nature should be selected for each woman individually.
It is not recommended to add progestin to the treatment regimen for patients without an intact uterus, unless endometriosis has been previously diagnosed.
Endometriosis Injections of the drug are used intramuscularly at a dose of 50 mg once a week or at a dose of 100 mg once every 2 weeks for at least 6 months.
Recurrent and / or metastatic breast cancer. The initial dose of medroxyprogesterone acetate is 500–1000 mg / day IM for 28 days. After this, the patient should be transferred to a maintenance schedule of use at a dose of 500 mg 2 times a week until a response to treatment is observed.
Recurrent and / or metastatic cancer of the endometrium or kidney. The recommended starting dose is 400–1000 mg / week IM. If improvement is noted within a few weeks or months and the disease has stabilized, maintenance of the improvement may be possible with the use of the drug in a lower dose of 400 mg once a month.
Metastatic prostate cancer. The initial dose of the drug is 500 mg / m 2 times a week for 3 months. The maintenance dose of the drug is 500 mg once a week.
Liver failure. No clinical studies have been conducted to evaluate the effect of liver disease on the pharmacokinetics of medroxyprogesterone acetate. However, it should be borne in mind that medroxyprogesterone acetate is almost completely excreted by the liver, and steroid hormones can be poorly metabolized in patients with severe liver failure.
Renal failure. No clinical studies have been conducted to evaluate the effect of kidney disease on the pharmacokinetics of medroxyprogesterone acetate. However, since medroxyprogesterone acetate is almost completely secreted by the liver, patients with renal failure do not need to adjust the dose of the drug.
The use of medroxyprogesterone acetate is contraindicated in patients with the following conditions:
- established or probable pregnancy;
- undiagnosed vaginal bleeding;
- severe liver dysfunction;
- known hypersensitivity to medroxyprogesterone acetate or other components of the drug.
Additional contraindications for use for contraception and for the treatment of endometriosis in dosages according to the indications:
- a known or suspected malignant neoplasm of the breast;
- A confirmed or suspected hormone-dependent genital tumor.
Very often - 10%, often ≥1 and 10%, infrequently - 0.1 and 1%, rarely - 0.1%, unknown (cannot be estimated from the available data).
|Organ system classes||Adverse reactions|
|Infections and infestations||Vaginitis|
|From the immune system||Hypersensitivity reactions (e.g. anaphylactic and anaphylactoid reactions, angioedema)|
|Endocrine system||Prolonged anovulation|
|On the part of metabolism, metabolism||Fluid retention, weight change|
|From the psyche||Depression, decreased libido or anorgasmia, insomnia, nervousness|
|From the nervous system||Cramps, dizziness, headache; infrequently - drowsiness, migraine; rarely - paralysis; unknown - syncope|
|From the vessels||Thromboembolic Disorders, Hot Flashes|
|From the gastrointestinal tract||Pain or discomfort in the abdomen, bloating, nausea; rarely rectal bleeding|
|From the liver||Jaundice|
|On the part of the skin and subcutaneous tissue||Acne, alopecia, hirsutism, pruritus, rash, urticaria; infrequently - chloasma, dermatitis, ecchymosis, melasma; unknown - striae, scleroderma|
|From the musculoskeletal system and connective tissue||Backache; infrequently - arthralgia, spasms of the calf muscles, pain in the limbs; unknown - armpit edema|
|From the reproductive system and mammary glands||Pathological uterine bleeding (irregular, intense, minor), amenorrhea, leukorrhea, pelvic pain, galactorrhea, mastodynia, tenderness of the mammary glands; infrequently - vaginal discharge, vulvovaginal dryness, changes in the size of the mammary glands, dyspareunia, ovarian cysts, premenstrual syndrome, genitourinary infections, uterine hyperplasia; rarely - nodes of the mammary glands or bleeding from the nipples; unknown - delayed lactation, onset of symptoms, as during pregnancy, loss of fertility|
|Benign, malignant and unspecified neoplasms (including cysts and polyps)||Rarely - breast cancer|
|On the part of the blood system and lymphatic system||Rarely - anemia; unknown - blood dysrasia|
|From the respiratory system, chest and mediastinal organs||Infrequently - shortness of breath|
|General disorders and changes at the injection site||Fatigue, asthenia, reactions at the injection site (pain / sensitivity, nodes / swelling, persistent atrophy / indentation / retraction of the skin, lipodystrophy), increased body temperature|
|Research||Decreased glucose tolerance, impaired liver function, decreased bone mineral density|
After the drug entered the market, patients receiving medroxyprogesterone acetate IM at a dose of 150 mg noted anaphylactic reactions, thromboembolic complications, and isolated cases of the development of